Method of treating Parkinson&#39;s disease with intranasal delivery of insulin and glutathione

ABSTRACT

A method for treating Parkinson&#39;s disease where insulin and GSH may be administered intranasally. The GSH and insulin that is administered may be in varying doses at least once daily. The GSH and insulin may be administered sequentially and/or simultaneously and the medications may be administered for differing periods of time depending upon a patient&#39;s tolerance and response to the GSH and insulin. The GSH and the insulin may be administered for a certain period of time and/or indefinitely.

CROSS-REFERENCE TO RELATED APPLICATION

This application is a divisional of U.S. patent application Ser.17/584,468, filed Jan. 26, 2022 and claims priority to U.S. ProvisionalPatent Application No. 63/153,422, filed Feb. 25, 2021, entitled “METHODOF TREATING PARKINSON′S DISEASE WITH INTRANASAL DELIVERY OF INSULIN ANDGLUTATHIONE,” the entirety of which is incorporated herein by reference.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

n/a

TECHNICAL FIELD

This disclosure relates to a method of treating neurological disordersand diseases by intranasal delivery of therapeutics.

INTRODUCTION

Parkinson's disease is a neurological disorder that affectsdopamine-producing neurons in a specific region of the brain, thesubstantia nigra. The disease is the second-most commonneurodegenerative disorder, and the incidence of Parkinson's diseaseincreases with age. The cause of the disease still remains largelyunknown and can be challenging to diagnose and manage. The disease ischronic and progressive, and no cure presently exists.

Some of the telltale symptoms of Parkinson's disease include rigidmuscles which can happen on almost any muscle in the body, slowmovements where simple acts, like buttoning a shirt, take much longerthan usual, tremors where certain portions of the body are shaky whenthey are not in use, walking and balance problems, as well as a host ofother issues including depression, constipation, anxiety, fatigue, sleepproblems, and bladder issues. These symptoms can affect every aspect ofthe life and can make day-to-day living very difficult.

Parkinson's disease cannot be cured currently, but some medications canhelp control the symptoms and make them more manageable. Presently, someof the available treatments can help with tremors, stuff muscles, andslow movements. Physical therapy, occupational therapy, speech therapy,surgery and other treatments are also available to try and manage thesymptoms. Additionally, eating certain foods and exercise can help calmsome of the symptoms of the disease.

The available medications to help treat and/or manage Parkinson'sdisease can have significant side-effects and patients have to work withtheir doctors to find a treatment plan that offers relief from symptomswith the fewest possible side effects. Determining the best treatmentplan for a patient often involves trial and error and results in acocktail of different medications and other treatments/therapies to helpease symptoms and improve the quality of life. Treatments for a patientmay evolve and change over time given the progressive nature ofParkinson's disease.

Medications for Parkinson's disease can be cumbersome and difficult totake. Additionally, with the complex behavioral changes related to thedisease, it can be difficult for a patient to routinely follow a giventreatment plan to try and lessen the symptoms of the disease.

SUMMARY

The present disclosure advantageously provides a method for thetreatment of Parkinson's disease, the method comprises: administeringglutathione (“GSH”) intranasally; and administering insulin and GSHintranasally.

In one aspect of the embodiment, the method may include GSH beingadministered intranasally at least once daily with a total dose of 400milligrams (“mg”) daily.

In one aspect of the embodiment, the method may include GSH beingadministered intranasally at least three times daily with a total doseof 400 mg daily.

In one aspect of the embodiment, the method may include GSH beingadministered intranasally with at least 280 mg per dose at least threetimes daily.

In one aspect of the embodiment, the method may include GSH beingadministered for at least ninety days.

In one aspect of the embodiment, the method may include insulin which isat least 40 International Units (“IU”).

In one aspect of the embodiment, the method may include insulinadministered intranasally at least once daily.

In one aspect of the embodiment, the method may include theadministration of insulin and GSH intranasally for at least twelveweeks.

In another embodiment, a method for the treatment of Parkinson's diseasecomprises administering GSH intranasally; and administering insulinintranasally.

In one aspect of the embodiment, the GSH may be intranasallyadministered at least two times daily.

In one aspect of the embodiment, at least 280 mg of GSH may beadministered intranasally at least two times daily.

In one aspect of the embodiment, the GSH and insulin may be administeredfor at least twelve weeks.

In one aspect of the embodiment, the insulin may be at least 40 IU.

In one aspect of the embodiment, the insulin may be administeredintranasally at least two times daily.

In one aspect of the embodiment, 20 IU of insulin may be administeredintranasally at least twice daily.

In one aspect of the embodiment, the administration of the insulin andthe GSH intranasally is for at least twenty-four weeks.

In yet another embodiment, a method for treating Parkinson's disease maycomprise administering GSH intranasally daily with at least two daily280 mg doses for at least twenty-four weeks; and administering insulin40 IU daily with at least two daily doses for at least twenty-fourweeks.

BRIEF DESCRIPTION OF THE DRAWINGS

A more complete understanding of the present disclosure, and theattendant advantages and features thereof, will be more readilyunderstood by reference to the following detailed description whenconsidered in conjunction with the accompanying drawings wherein:

FIG. 1 shows an exemplary method for the treatment of Parkinson'sdisease;

FIG. 2 shows an exemplary method for the treatment of Parkinson'sdisease; and

FIG. 3 shows an exemplary method for the treatment of Parkinson'sdisease.

DETAILED DESCRIPTION

Before describing in detail exemplary embodiments, it is noted that theembodiments reside primarily in combinations of methods related totreating neurological diseases, including Parkinson's disease, withintranasal delivery of insulin and glutathione (“GSH”). Accordingly, thesystem and method components have been represented where appropriate byconventional symbols in the drawings, showing only those specificdetails that are pertinent to understanding the embodiments of thepresent disclosure so as not to obscure the disclosure with details thatwill be readily apparent to those of ordinary skill in the art havingthe benefit of the description herein.

As used herein, relational terms, such as “first” and “second,” “top”and “bottom,” and the like, may be used solely to distinguish one entityor element from another entity or element without necessarily requiringor implying any physical or logical relationship or order between suchentities or elements. The terminology used herein is for the purpose ofdescribing particular embodiments only and is not intended to belimiting of the concepts described herein. As used herein, the singularforms “a”, “an” and “the” are intended to include the plural forms aswell, unless the context clearly indicates otherwise. It will be furtherunderstood that the terms “comprises,” “comprising,” “includes” and/or“including” when used herein, specify the presence of stated features,integers, steps, operations, elements, and/or components, but do notpreclude the presence or addition of one or more other features,integers, steps, operations, elements, components, and/or groupsthereof.

Unless otherwise defined, all terms (including technical and scientificterms) used herein have the same meaning as commonly understood by oneof ordinary skill in the art to which this disclosure belongs. It willbe further understood that terms used herein should be interpreted ashaving a meaning that is consistent with their meaning in the context ofthis specification and the relevant art and will not be interpreted inan idealized or overly formal sense unless expressly so defined herein.

The embodiments provide systems and methods for treating patients withneurological disorders, including Parkinson's disease (“PD”), with GSHand insulin. PD is a common chronic neurodegenerative disease that isoften treated with different pharmaceutical agents intended to try andlessen some of the symptoms temporarily. Evidence has indicated thatinsulin may influence several processes in the brain includingmaintenance of synapses and pathways involving cogitation. GSH may serveas an important antioxidant, particularly in patients with PD, which isimportant for maintaining redox homeostasis, clearing metabolic waste,and serving as a reservoir for amino acids in the central nervous system(“CNS”).

Referring now to the drawings in which like reference designators referto like elements, there is shown in FIG. 1 an exemplary method inaccordance with the principles of the present application. In FIG. 1 ,there are various steps shown in the exemplary method for the treatmentof Parkinson's disease where S110 refers to step 1 of the method, S120refers to step 2 of the method, and S130 refers to step 3 of the method.The method for the treatment of Parkinson's disease S110 may includeadministering GSH intranasally S120. GSH may be a tripeptide comprisedof cysteine, glutamic acid, and glycine and is generally present in mostmammalian tissue. GSH may function as an antioxidant, a free radicalscavenger, and a detoxifying agent.

GSH may be administered in a variety of different manners including, butnot limited to, intravenously by injection, orally, and intranasally. Asa non-limiting example of how GSH may be administered, a ViaNase™Electronic Atomizer may be used for an intranasal delivery of medicationor GSH may be nebulized or aerosolized as well.

The intranasal administration of the medicine may include aerosol in amist and/or larger droplets as administration using an aerosol may havefavorable pharmacokinetics in terms of central nervous systempenetration. For example, intranasal administration may allow the GSH tobypass the blood-brain barrier via the nasal cavity. The vascular makeupof the nasal cavity provides a route into the blood stream formedications that easily cross mucous membranes. Additionally, the directabsorption of medication into the blood stream may avoidgastrointestinal destruction and destruction of drugs by liver enzymes.Accordingly, the intranasal delivery of GSH as well as other drugs maymake the drug more effective in the body. Furthermore, the rates ofabsorption of intranasal medications are typically better thansubcutaneous or intramuscular routes. It may also be safer, easier, andmore convenient for patients to take a medication intranasally,especially those that have an altered mental status.

Different doses of the GSH may be administered to a patient. As anon-limiting example, one dose may be administered to a patient ormultiple doses may be administered. In an exemplary embodiment, thepatient may receive two daily doses with 280 milligrams (“mg”) of GSHper dose intranasally with a total of 400 mg of GSH daily or the patientmay receive three daily doses of GSH intranasally with a total of 400 mgof GSH daily. Alternatively, the patient may receive three dailyintranasal doses of 280 mg per dose with a total dose of 600 mg of GSHdaily. More or less daily doses may be received by the patient and thetotal mg of GSH administered to the patient may also vary depending uponthe patient's response to the GSH. The GSH may be administered using thesame mg dosing daily or a varying mg dosing each day. For example, in apatient receiving two daily doses, one dose may be for 100 mg of GSH anda second dose of GSH may be for 300 mg of GSH. Additionally, a patientmay receive different doses of GSH daily, for example, receiving 400 mgof GSH on one day and then receiving 600 mg of GSH on another day.Sensitivity and responsiveness to the GSH may drive when and how GSHdosing is provided to a patient.

The GSH may be administered to the patient over varying amounts of time.For example, the patient may receive GSH over a period of time tounderstand the safety, efficacy, and tolerability of the medication forthe patient. The GSH may be administered for a certain period of timeand/or indefinitely. In an exemplary embodiment, the GSH may beadministered for a period of ninety days to evaluate a patient'sresponse to the administration. Varying amounts of time may be used toadminister the medication and could be significantly less or more timethan ninety days. If a patient is not tolerating the GSH, the patientmay either stop taking the GSH temporarily or alternatively may stop themedication permanently. Additionally, the amount of GSH given to thepatient intranasally may vary depending on patient tolerance.

Also, insulin and GSH may be administered intranasally S130 to thepatient. This may occur before, at the same time, or after theadministration of the GSH intranasally. Insulin may play a role inregulating neuronal survival and growth, dopaminergic transmission, andin the maintenance of synapses. Different strengths and types of insulinmay be used. As a non-limiting example, human insulin may be used whichis created using DNA recombinant technology. In an exemplary embodiment,insulin at a strength of 40 International Units/milliliter (“IU/ml”) orinsulin at a strength of 20 IU/ml, 160 IU/ml, 100 IU/ml or 500 IU/ml maybe used. The strength of the insulin used may depend on the patient'stolerance to insulin. Additionally, varying doses of insulin may be useddepending upon the requirements of the particular patient. For example,a patient may be resistant to insulin, have diabetes, or another medicalcondition which may impact when, how, and how much insulin isadministered.

The insulin may be delivered intranasally but may also be delivered viaan injection using a syringe, injection pen, an insulin pump, or orally.The intranasal delivery of insulin may enhance long-term memory of aperson and positively affect mood. Intranasal insulin administration mayalso result in direct insulin transport from the nasal cavity to thecentral nervous system via intraneuronal and extraneurnal pathways. Inan exemplary embodiment, 20 IU of insulin may be delivered intranasallyin two daily doses or 40 IU of insulin may be delivered in one dailydose. In alternative embodiments, the insulin may be delivered indifferent strengths and may be given in greater or fewer than two dailydoses.

The administration of the GSH and insulin intranasally may be done overdiffering periods of times depending on the patient's response andtolerance to the medications. The GSH and insulin may be administered ina variety of different ways for a certain period of time and/orindefinitely. As a non-limiting example, the GSH and the insulin may beadministered intranasally for a period of at least twelve weeks. The GSHand insulin may also be administered over differing periods of time. Forexample, the GSH may also be administered intranasally for twelve weeksand the insulin may be administered intranasally for fourteen weeks.

When the GSH and insulin are administered to the patient, the GSH may begiven to a patient in varying amounts and one time daily or more thanone time daily. The insulin and the GSH may be administered sequentiallyand/or simultaneously. For example, the GSH and insulin may beadministered intranasally together, the GSH may be administeredintranasally and then the insulin may be administered intranasally tothe patient, or the insulin may be administered intranasally and thenthe GSH may be administered intranasally to the patient.

In an exemplary embodiment, the GSH may be administered intranasally intwo daily doses. 280 mg of GSH may be administered to the patient ineach dose totaling 400 mg of GSH in one day. The GSH may not beadministered in the same dosing each time and different doses may beused throughout the day or may be changed depending upon the patient'sresponse to the medication. As a non-limiting example, GSH may beadministered intranasally at least once daily with a total dose of 400mg daily, the GSH may be administered intranasally at least two timesdaily with a total dose of 400 mg daily, or the GSH may by administeredintranasally with at least 280 mg per dose at least two times daily.

Referring now to FIG. 2 , in this embodiment, there are various stepsshown in the exemplary method for the treatment of Parkinson's diseasewhere S140 refers to step 1 of the method, S150 refers to step 2 of themethod, and S160 refers to step 3 of the method. The method for thetreatment of PD S140 may include administering GSH intranasally S150 andadministering insulin intranasally S160. The GSH and insulin may bedelivered intranasally simultaneously and/or sequentially, such that theGSH and insulin may be administered intranasally together, the GSH maybe administered intranasally and then insulin may be administeredintranasally to the patient, or the insulin may be administeredintranasally and then the GSH may be administered intranasally to thepatient.

As a non-limiting example, the GSH that is administered may be done atleast two times daily wherein at least 280 mg is administeredintranasally in each dose. The GSH may be administered for at leasttwelve weeks, but the time period may be longer or shorter as well.

The insulin may be 40 IU, but different strengths and types of insulinmay be used depending upon a patient's tolerance to insulin and thepatient's response to the insulin. For example, insulin may beadministered intranasally at least twice daily, but this may be more orless frequent depending upon the particular patient and theirsensitivity and/or responsiveness to the insulin. The administration ofthe insulin and the GSH may be for at least a period of twenty-fourweeks, but it may also be a longer or shorter period of time dependingupon the particular patient.

Referring now to FIG. 3 , in this embodiment, there are various stepsshown in the exemplary method for the treatment of Parkinson's diseasewhere S170 refers to step 1 of the method, S180 refers to step 2 of themethod, and S190 refers to step 3 of the method. The method for thetreatment of Parkinson's disease S170 may include administering GSHintranasally daily with at least two daily 280 mg doses for at leasttwenty-four weeks S180 and administering insulin 40 IU intranasallydaily with at least two daily doses for at least twenty-four weeks S190.The GSH and the insulin may be administered together or at differenttimes. Additionally, the dosing of the GSH and the insulin may bevariable depending upon the particular patient.

It will be appreciated by persons skilled in the art that the presentembodiments are not limited to what has been particularly shown anddescribed herein above. In addition, unless mention was made above tothe contrary, it should be noted that all of the accompanying drawingsare not to scale. A variety of modifications and variations are possiblein light of the above teachings.

What is claimed:
 1. A method for the treatment of Parkinson's disease,the method comprising: administering at least 200 milligrams (“mg”) ofglutathione (“GSH”) intranasally at least once daily; and administering20 international units (“IU”) of insulin bid and at least 100 mg of GSHintranasally at least twice daily.
 2. The method of claim 1, wherein thetotal GSH dose administered daily is at least 400 mg.
 3. The method ofclaim 1, wherein the GSH is administered for at least ninety days. 4.The method of claim 1, wherein the administration of the insulin and GSHintranasally is for at least twelve weeks.